ArticleAmerican journal of respiratory cell and molecular biology2015
Role of Krev Interaction Trapped-1 in Prostacyclin-Induced Protection against Lung Vascular Permeability Induced by Excessive Mechanical Forces and Thrombin Receptor Activating Peptide 6.
Article in American journal of respiratory cell and molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Ventilator-Induced Lung Injury: Mechanotransduction and Potential Therapeutic Targets.MedComm · 2026Review
- Pulmonary arterial hypertension drugs can partially restore altered angiogenic capacities inPulmonary circulation · 2023Article
- mPR-Specific Actions Influence Maintenance of the Blood-Brain Barrier (BBB).International journal of molecular sciences · 2022Article
- Mechanisms of Mechanical Force Induced Pulmonary Vascular Endothelial Hyperpermeability.Frontiers in physiology · 2021Review
- Identification and Functional Analysis of Long Non-coding RNAs in Human Pulmonary Microvascular Endothelial Cells Subjected to Cyclic Stretch.Frontiers in physiology · 2021Article
- Cerebral Cavernous Malformation Proteins in Barrier Maintenance and Regulation.International journal of molecular sciences · 2020Review
- RhoGTPase in Vascular Disease.Cells · 2019Review
- Mechanosensitive Rap1 activation promotes barrier function of lung vascular endothelium under cyclic stretch.Molecular biology of the cell · 2019Article
- Rap1 in endothelial biology.Current opinion in hematology · 2017Review
- Perioperative "remote" acute lung injury: recent update.Journal of biomedical research · 2017Article
- Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin.The international journal of biochemistry & cell biology · 2016Review
- Introduction to cerebral cavernous malformation: a brief review.BMB reports · 2016Review
- Cytochrome P450 and matrix metalloproteinase genetic modifiers of disease severity in Cerebral Cavernous Malformation type 1.Free radical biology & medicine · 2016Article
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6 authors at 1 institution in 1 country.
Funding
Abstract
Mechanisms of vascular endothelial cell (EC) barrier regulation during acute lung injury (ALI) or other pathologies associated with increased vascular leakiness are an active area of research. Adaptor protein krev interaction trapped-1 (KRIT1) participates in angiogenesis, lumen formation, and stabilization of EC adherens junctions (AJs) in mature vasculature. We tested a role of KRIT1 in the regulation of Rho-GTPase signaling induced by mechanical stimulation and barrier dysfunction relevant to ventilator-induced lung injury and investigated KRIT1 involvement in EC barrier protection by prostacyclin (PC). PC stimulated Ras-related protein 1 (Rap1)-dependent association of KRIT1 with vascular endothelial cadherin at AJs, with KRIT1-dependent cortical cytoskeletal remodeling leading to EC barrier enhancement. KRIT1 knockdown exacerbated Rho-GTPase activation and EC barrier disruption induced by pathologic 18% cyclic stretch and thrombin receptor activating peptide (TRAP) 6 and attenuated the protective effects of PC. In the two-hit model of ALI caused by high tidal volume (HTV) mechanical ventilation and TRAP6 injection, KRIT1 functional deficiency in KRIT1(+/-) mice increased basal lung vascular leak and augmented vascular leak and lung injury caused by exposure to HTV and TRAP6. Down-regulation of KRIT1 also diminished the protective effects of PC against TRAP6/HTV-induced lung injury. These results demonstrate a KRIT1-dependent mechanism of vascular EC barrier control in basal conditions and in the two-hit model of ALI caused by excessive mechanical forces and TRAP6 via negative regulation of Rho activity and enhancement of cell junctions. We also conclude that the stimulation of the Rap1-KRIT1 signaling module is a major mechanism of vascular endothelial barrier protection by PC in the injured lung.
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